Evaluating Panitumumab (ABX-EGF) Monotherapy in Patients With Metastatic Colorectal Cancer Following Treatment With Fluoropyrimidine, Irinotecan, and Oxaliplatin Chemotherapy

• ClinicalTrials.gov Identifier: NCT00083616
• Recruitment Status: Completed
• First Posted: May 28, 2004
• Results First Posted: July 29, 2011
• Last Update Posted: January 10, 2014
• Sponsor: Amgen
• Information provided by (Responsible Party): Amgen

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Conditions: Colorectal Cancer; Metastatic Cancer
• Intervention: Biological: Panitumumab
• Enrollment: 185

Participant Flow

Recruitment Details	Participants were enrolled from 1 March 2004 through 19 Jul 2006. Patient disposition is reported up until the data cut-off date of 22 December 2006. Completed study is defined as participants who either died on study or completed the safety follow-up visit (30 days after the last dose of panitumumab).
Pre-assignment Details

Arm/Group Title	Panitumumab (ABX-EGF)
Arm/Group Description	Open-label panitumumab administered by intravenous (IV) infusion at a dose of 6 mg/kg given once every 2 weeks until participants developed progressive disease, were unable to tolerate panitumumab, or discontinued treatment for other reasons.
Period Title: Overall Study
Started	185
Received Study Medication	182
Completed	154 [1]
Not Completed	31
Reason Not Completed
Disease Progression	16
Lost to Follow-up	1
Physician Decision	2
Withdrawal by Subject	3
Ineligibility determined	2
Non-compliance	1
Other	6
[1] Completed safety followup or died on study as of the data cut-off date of 22 December 2006

Baseline Characteristics

Arm/Group Title		Panitumumab
Arm/Group Description		Open-label panitumumab administered by intravenous (IV) infusion at a dose of 6 mg/kg given once every 2 weeks until participants developed progressive disease, were unable to tolerate panitumumab, or discontinued treatment for other reasons.
Overall Number of Baseline Participants		185
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	185 participants
		59.6 (10.6)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	185 participants
	Female	85 45.9%
	Male	100 54.1%
Race/Ethnicity, Customized; Measure Type: Number; Unit of measure: Participants	Number Analyzed	185 participants
American Indian or Alaska Native		0
Asian		4
Black or African American		15
Hispanic or Latino		19
Japanese		0
Native Hawaiian or Other Pacific Islander		1
White or Caucasian		144
Other		2
Aborigine		0

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Objective Tumor Response Through Week 16
Description	Confirmed objective tumor response (complete or partial response) based on modified World Health Organization (WHO) criteria, through week 16. Tumor response was assessed by a central Independent Review Committee (IRC) and confirmation 4 weeks after initial assessment was required. Complete Response (CR): Disappearance of all index and non-index lesions and no new lesions. Partial Response (PR): At least a 50% decrease in the sum of the product of the longest diameters (SPD) of index lesions taking as reference the Baseline SPD, and no new non-index lesions and no "unequivocal progression" of non-index lesions, or, the disappearance of all index lesions and persistence of one or more non-index lesions not qualifying for either CR or Progressive Disease.
Time Frame	16 weeks

Outcome Measure Data

Analysis Population Description

Adjudicated Prior Failures Set, composed of participants confirmed to be eligible by the Independent Eligibility Review Committee (IERC)

Arm/Group Title	Panitumumab
Arm/Group Description:	Open-label panitumumab administered by intravenous (IV) infusion at a dose of 6 mg/kg given once every 2 weeks until participants developed progressive disease, were unable to tolerate panitumumab, or discontinued treatment for other reasons.
Overall Number of Participants Analyzed	142
Measure Type: Number; Unit of Measure: Participants
	5

2. Primary Outcome

Title	Duration of Response
Description	The time from first objective response to first observed progression of disease or death if the death was due to disease progression (whichever comes first); participants who respond and have not progressed while on study or died for reasons other than disease progression while on study were censored at their last evaluable disease assessment date. Response (complete or partial response) was assessed per modified WHO criteria by the central IRC. Complete Response (CR): Disappearance of all index and non-index lesions and no new lesions. Partial Response (PR): At least a 50% decrease in the sum of the product of the longest diameters (SPD) of index lesions taking as reference the Baseline SPD, and no new non-index lesions and no "unequivocal progression" of non-index lesions, or, the disappearance of all index lesions and persistence of one or more non-index lesions not qualifying for either CR or Progressive Disease.
Time Frame	Until the data cut-off date of 22 December 2006. Maximum time of follow-up was 128 weeks.

Outcome Measure Data

Analysis Population Description

Subset of the Adjudicated Prior Failures Set, composed of participants confirmed to be eligible by the Independent Eligibility Review Committee (IERC), who had a confirmed obective tumor response

Arm/Group Title	Panitumumab
Arm/Group Description:	Open-label panitumumab administered by intravenous (IV) infusion at a dose of 6 mg/kg given once every 2 weeks until participants developed progressive disease, were unable to tolerate panitumumab, or discontinued treatment for other reasons.
Overall Number of Participants Analyzed	5
Median (95% Confidence Interval); Unit of Measure: Weeks
	14.0; (12.4 to 101.7)

3. Secondary Outcome

Title	Number of Participants With Objective Tumor Response Throughout Study
Description	Confirmed objective tumor response (complete or partial response) based on modified World Health Organization (WHO) criteria, throughout the duration of the study Tumor response was assessed by a central Independent Review Committee (IRC) and confirmation 4 weeks after initial assessment was required. Complete Response (CR): Disappearance of all index and non-index lesions and no new lesions. Partial Response (PR): At least a 50% decrease in the sum of the product of the longest diameters (SPD) of index lesions taking as reference the Baseline SPD, and no new non-index lesions and no "unequivocal progression" of non-index lesions, or, the disappearance of all index lesions and persistence of one or more non-index lesions not qualifying for either CR or Progressive Disease.
Time Frame	Until the data cut-off date of 22 December 2006. Maximum time of follow-up was 128 weeks.

Outcome Measure Data

Analysis Population Description

Adjudicated Prior Failures Set, composed of participants confirmed to be eligible by the Independent Eligibility Review Committee (IERC)

Arm/Group Title	Panitumumab
Arm/Group Description:	Open-label panitumumab administered by intravenous (IV) infusion at a dose of 6 mg/kg given once every 2 weeks until participants developed progressive disease, were unable to tolerate panitumumab, or discontinued treatment for other reasons.
Overall Number of Participants Analyzed	142
Measure Type: Number; Unit of Measure: Participants
	5

4. Secondary Outcome

Title	Time to Response
Description	Median time from enrollment to objective tumor response for participants who responded.
Time Frame	Until the data cut-off date of 22 December 2006. Maximum time of follow-up was 128 weeks.

Outcome Measure Data

Analysis Population Description

Subset of Adjudicated Prior Failures Set, composed of participants confirmed to be eligible by the Independent Eligibility Review Committee (IERC), who had a confirmed objective tumor response

Arm/Group Title	Panitumumab
Arm/Group Description:	Open-label panitumumab administered by intravenous (IV) infusion at a dose of 6 mg/kg given once every 2 weeks until participants developed progressive disease, were unable to tolerate panitumumab, or discontinued treatment for other reasons.
Overall Number of Participants Analyzed	5
Median (Inter-Quartile Range); Unit of Measure: Weeks
	11.0; (7.7 to 11.1)

5. Secondary Outcome

Title	Progression-free Survival Time
Description	Kaplan-Meier estimate of median time from enrollment to death or first observed disease progression (whichever comes first). Participants who did not progress while on study and did not die while on study were censored at the last evaluable disease assessment date.
Time Frame	Until the data cut-off date of 22 December 2006. Maximum follow-up time was 128 weeks.

Outcome Measure Data

Analysis Population Description

Adjudicated Prior Failures Set, composed of participants confirmed to be eligible by the Independent Eligibility Review Committee (IERC)

Arm/Group Title	Panitumumab
Arm/Group Description:	Open-label panitumumab administered by intravenous (IV) infusion at a dose of 6 mg/kg given once every 2 weeks until participants developed progressive disease, were unable to tolerate panitumumab, or discontinued treatment for other reasons.
Overall Number of Participants Analyzed	142
Median (95% Confidence Interval); Unit of Measure: Weeks
	7.3; (7.1 to 7.4)

6. Secondary Outcome

Title	Time to Disease Progression
Description	Kaplan-Meier estimate of the median time from enrollment to first observed disease progression or death if death was due to disease progression (whichever comes first). Participants who did not progress while on study or died for reasons other than disease progression while on study were censored at their last evaluable disease assessment date.
Time Frame	Until the data cut-off date of 22 December 2006. Maximum follow-up time was 128 weeks.

Outcome Measure Data

Analysis Population Description

Adjudicated Prior Failures Set, composed of participants confirmed to be eligible by the Independent Eligibility Review Committee (IERC)

Arm/Group Title	Panitumumab
Arm/Group Description:	Open-label panitumumab administered by intravenous (IV) infusion at a dose of 6 mg/kg given once every 2 weeks until participants developed progressive disease, were unable to tolerate panitumumab, or discontinued treatment for other reasons.
Overall Number of Participants Analyzed	142
Median (95% Confidence Interval); Unit of Measure: Weeks
	7.3; (7.1 to 7.6)

7. Secondary Outcome

Title	Time to Treatment Failure
Description	Kaplan-Meier estimate of median time from enrollment to treatment failure, defined as the date the decision was made to end treatment. Participants remaining in the treatment phase at the time of the analysis were censored on their last visit date.
Time Frame	Until the data cut-off date of 22 December 2006. Maximum follow-up time was 128 weeks.

Outcome Measure Data

Analysis Population Description

Adjudicated Prior Failures Set, composed of participants confirmed to be eligible by the Independent Eligibility Review Committee (IERC)

Arm/Group Title	Panitumumab
Arm/Group Description:	Open-label panitumumab administered by intravenous (IV) infusion at a dose of 6 mg/kg given once every 2 weeks until participants developed progressive disease, were unable to tolerate panitumumab, or discontinued treatment for other reasons.
Overall Number of Participants Analyzed	142
Median (95% Confidence Interval); Unit of Measure: Weeks
	8.0; (7.4 to 8.1)

8. Secondary Outcome

Title	Duration of Stable Disease
Description	Kaplan-Meier estimates of the median time from enrollment to the date of first observed disease progression or death due to disease progression among those participants with a best outcome of stable disease. Stable disease (SD): Neither sufficient shrinkage of Index lesions to qualify for partial response nor sufficient increase to qualify for progressive disease (PD) taking as reference the nadir sum of the products of the longest diameters (SPD) since the treatment started and the disappearance of or persistence of one or more non-index lesions not qualifying for PD.
Time Frame	Until the data cut-off date of 22 December 2006. Maximum follow-up time was 128 weeks.

Outcome Measure Data

Analysis Population Description

Subset of Adjudicated Prior Failures Set, composed of participants confirmed to be eligible by the Independent Eligibility Review Committee (IERC), with a best outcome of stable disease

Arm/Group Title	Panitumumab
Arm/Group Description:	Open-label panitumumab administered by intravenous (IV) infusion at a dose of 6 mg/kg given once every 2 weeks until participants developed progressive disease, were unable to tolerate panitumumab, or discontinued treatment for other reasons.
Overall Number of Participants Analyzed	31
Median (95% Confidence Interval); Unit of Measure: Weeks
	23.9; (23.0 to 31.0)

9. Secondary Outcome

Title	Overall Survival
Description	Kaplan-Meier estimate of median time from enrollment to death from any cause. Deaths were recorded during treatment, safety follow-up and long term follow-up.
Time Frame	Until the data cut-off date of 22 December 2006. Maximum follow-up time was 128 weeks.

Outcome Measure Data

Analysis Population Description

Adjudicated Prior Failures Set, composed of participants confirmed to be eligible by the Independent Eligibility Review Committee (IERC)

Arm/Group Title	Panitumumab
Arm/Group Description:	Open-label panitumumab administered by intravenous (IV) infusion at a dose of 6 mg/kg given once every 2 weeks until participants developed progressive disease, were unable to tolerate panitumumab, or discontinued treatment for other reasons.
Overall Number of Participants Analyzed	142
Median (95% Confidence Interval); Unit of Measure: months
	7.0; (5.7 to 8.0)

Adverse Events

Time Frame	From the first dose through maximum of safety follow-up or 30 days after last dose; maximum time on study treatment was 1.25 years.
Adverse Event Reporting Description	The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Arm/Group Title	Panitumumab
Arm/Group Description	[Not Specified]
All-Cause Mortality
	Panitumumab
	Affected / at Risk (%)
Total	--/--
Serious Adverse Events
	Panitumumab
	Affected / at Risk (%)
Total	62/182 (34.07%)
Blood and lymphatic system disorders
Anaemia † 1	1/182 (0.55%)
Cardiac disorders
Atrial fibrillation † 1	1/182 (0.55%)
Cardiac failure congestive † 1	1/182 (0.55%)
Gastrointestinal disorders
Abdominal distension † 1	3/182 (1.65%)
Abdominal hernia † 1	1/182 (0.55%)
Abdominal pain † 1	4/182 (2.20%)
Abdominal pain lower † 1	1/182 (0.55%)
Ascites † 1	3/182 (1.65%)
Colonic fistula † 1	1/182 (0.55%)
Constipation † 1	1/182 (0.55%)
Diarrhoea † 1	1/182 (0.55%)
Duodenal obstruction † 1	1/182 (0.55%)
Gastrointestinal haemorrhage † 1	1/182 (0.55%)
Intestinal obstruction † 1	2/182 (1.10%)
Nausea † 1	2/182 (1.10%)
Pancreatitis † 1	1/182 (0.55%)
Pancreatitis acute † 1	1/182 (0.55%)
Reflux oesophagitis † 1	1/182 (0.55%)
Small intestinal obstruction † 1	6/182 (3.30%)
Vomiting † 1	2/182 (1.10%)
General disorders
Early satiety † 1	1/182 (0.55%)
Fatigue † 1	1/182 (0.55%)
Pain † 1	1/182 (0.55%)
Hepatobiliary disorders
Bile duct obstruction † 1	2/182 (1.10%)
Cholangitis † 1	1/182 (0.55%)
Hepatic function abnormal † 1	1/182 (0.55%)
Hyperbilirubinaemia † 1	1/182 (0.55%)
Jaundice cholestatic † 1	1/182 (0.55%)
Immune system disorders
Hypersensitivity † 1	1/182 (0.55%)
Infections and infestations
Bacteraemia † 1	1/182 (0.55%)
Catheter related infection † 1	1/182 (0.55%)
Cellulitis † 1	1/182 (0.55%)
Endocarditis staphylococcal † 1	1/182 (0.55%)
Folliculitis † 1	1/182 (0.55%)
Lobar pneumonia † 1	1/182 (0.55%)
Pneumonia † 1	3/182 (1.65%)
Pneumonia bacterial † 1	1/182 (0.55%)
Pyelonephritis † 1	1/182 (0.55%)
Septic embolus † 1	1/182 (0.55%)
Septic shock † 1	1/182 (0.55%)
Urosepsis † 1	1/182 (0.55%)
Injury, poisoning and procedural complications
Humerus fracture † 1	1/182 (0.55%)
Lumbar vertebral fracture † 1	1/182 (0.55%)
Investigations
Weight decreased † 1	1/182 (0.55%)
Metabolism and nutrition disorders
Cachexia † 1	1/182 (0.55%)
Dehydration † 1	2/182 (1.10%)
Diabetes mellitus inadequate control † 1	1/182 (0.55%)
Fluid retention † 1	1/182 (0.55%)
Hyperkalaemia † 1	1/182 (0.55%)
Hypocalcaemia † 1	1/182 (0.55%)
Hypokalaemia † 1	2/182 (1.10%)
Hypomagnesaemia † 1	1/182 (0.55%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer † 1	6/182 (3.30%)
Colon cancer metastatic † 1	6/182 (3.30%)
Colorectal cancer † 1	5/182 (2.75%)
Metastases to central nervous system † 1	1/182 (0.55%)
Neoplasm progression † 1	1/182 (0.55%)
Rectal cancer metastatic † 1	2/182 (1.10%)
Nervous system disorders
Anoxic encephalopathy † 1	1/182 (0.55%)
Convulsion † 1	2/182 (1.10%)
Dizziness † 1	1/182 (0.55%)
Hepatic encephalopathy † 1	1/182 (0.55%)
Speech disorder † 1	1/182 (0.55%)
Spinal cord compression † 1	1/182 (0.55%)
Vocal cord paralysis † 1	1/182 (0.55%)
Psychiatric disorders
Anxiety † 1	2/182 (1.10%)
Confusional state † 1	1/182 (0.55%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure † 1	1/182 (0.55%)
Bronchial obstruction † 1	1/182 (0.55%)
Dyspnoea † 1	7/182 (3.85%)
Hypoxia † 1	2/182 (1.10%)
Pleural effusion † 1	3/182 (1.65%)
Pneumothorax † 1	1/182 (0.55%)
Pulmonary embolism † 1	1/182 (0.55%)
Pulmonary oedema † 1	1/182 (0.55%)
Respiratory arrest † 1	1/182 (0.55%)
Respiratory distress † 1	1/182 (0.55%)
Respiratory failure † 1	4/182 (2.20%)
Vascular disorders
Circulatory collapse † 1	1/182 (0.55%)
Deep vein thrombosis † 1	3/182 (1.65%)
Hypotension † 1	1/182 (0.55%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 11.0
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Panitumumab
	Affected / at Risk (%)
Total	176/182 (96.70%)
Gastrointestinal disorders
Abdominal pain † 1	34/182 (18.68%)
Ascites † 1	11/182 (6.04%)
Constipation † 1	36/182 (19.78%)
Diarrhoea † 1	48/182 (26.37%)
Dyspepsia † 1	12/182 (6.59%)
Nausea † 1	58/182 (31.87%)
Stomatitis † 1	16/182 (8.79%)
Vomiting † 1	38/182 (20.88%)
General disorders
Asthenia † 1	12/182 (6.59%)
Chills † 1	11/182 (6.04%)
Fatigue † 1	66/182 (36.26%)
Oedema peripheral † 1	17/182 (9.34%)
Pyrexia † 1	23/182 (12.64%)
Infections and infestations
Paronychia † 1	32/182 (17.58%)
Rash pustular † 1	16/182 (8.79%)
Urinary tract infection † 1	13/182 (7.14%)
Investigations
Weight decreased † 1	19/182 (10.44%)
Metabolism and nutrition disorders
Anorexia † 1	31/182 (17.03%)
Decreased appetite † 1	11/182 (6.04%)
Dehydration † 1	12/182 (6.59%)
Hypokalaemia † 1	15/182 (8.24%)
Hypomagnesaemia † 1	20/182 (10.99%)
Musculoskeletal and connective tissue disorders
Back pain † 1	21/182 (11.54%)
Pain in extremity † 1	10/182 (5.49%)
Nervous system disorders
Dizziness † 1	12/182 (6.59%)
Headache † 1	18/182 (9.89%)
Psychiatric disorders
Anxiety † 1	14/182 (7.69%)
Depression † 1	10/182 (5.49%)
Insomnia † 1	16/182 (8.79%)
Respiratory, thoracic and mediastinal disorders
Cough † 1	24/182 (13.19%)
Dyspnoea † 1	29/182 (15.93%)
Skin and subcutaneous tissue disorders
Acne † 1	10/182 (5.49%)
Dermatitis acneiform † 1	125/182 (68.68%)
Dry skin † 1	28/182 (15.38%)
Erythema † 1	112/182 (61.54%)
Exfoliative rash † 1	30/182 (16.48%)
Nail disorder † 1	15/182 (8.24%)
Pruritus † 1	96/182 (52.75%)
Rash † 1	44/182 (24.18%)
Rash papular † 1	12/182 (6.59%)
Skin exfoliation † 1	17/182 (9.34%)
Skin fissures † 1	24/182 (13.19%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 11.0

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.

Results Point of Contact

• Name/Title: Study Director
• Organization: Amgen Inc.
• Phone: 866-572-6436

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Liao MZ, Prenen H, Dutta S, Upreti VV. The impact of hepatic and renal function on panitumumab exposures in patients with metastatic RAS wild-type colorectal cancer. Cancer Chemother Pharmacol. 2021 Oct;88(4):665-672. doi: 10.1007/s00280-021-04319-w. Epub 2021 Jul 2.

• Responsible Party: Amgen
• ClinicalTrials.gov Identifier: NCT00083616
• Obsolete Identifiers: NCT00087243
• Other Study ID Numbers: 20030167
• First Submitted: May 26, 2004
• First Posted: May 28, 2004
• Results First Submitted: August 6, 2010
• Results First Posted: July 29, 2011
• Last Update Posted: January 10, 2014